COVID-19, Sars-CoV2
Conditions
Keywords
COVID-19, Sars-CoV2, Convalescent plasma
Brief summary
The purpose of this study assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms up to 14 days after the onset of initial symptoms.
Detailed description
A total of 50 eligible subjects will be randomized in a 1:1 ratio to receive either convalescent fresh frozen plasma (frozen within 8 hours of collection) of PF24 (frozen within 24 hours) from blood donors who have recovered from COVID-19 containing antibodies to SARS-CoV-2 or control (standard fresh frozen plasma collected prior to 12/1/2019 or with documented negative SARS-CoV-2 antibody). Should additional anti-COVID agents (anti-viral and/or anti-inflammatory) become available for use as standard of care during implementation, the sample size will be recalculated and increased to account for the estimated impact that these agents may have on the reducing the progression to the primary endpoint of severe hypoxemia.
Interventions
BIOLOGICALCOVID-19 Convalescent Plasma (CCP)
COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.
BIOLOGICALPlacebo
Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.
Sponsors
Vitalant Research Institute
San Francisco General Hospital
Priscilla Hsue, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Study investigators analyzing the data and participants will be blinded to the randomization. It may not be feasible to blind nursing staff to the treatment assignment to ensure proper ABO checking of the plasma unit at bedside per standard transfusion procedures, but every effort will be made to preserve blinding of the investigators, participant, and primary team providing care. An unblinded research assistant who is not involved in other aspects of the study will randomize the participant once enrolled. Randomization will be provided to an unblinded provider who is not part of the care team who will place the order for the plasma (CCP vs. control plasma) using a paper order that will not be part of the electronic medical record. The safety monitoring committee (SMC) will review study data, including unblinded data, to evaluate the safety, efficacy, study progress, and conduct of the study.
Intervention model description
Subjects enrolled in the study will be randomized using a web based randomization procedure to receive convalescent plasma versus non-immune plasma at a 1:1 ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for Enrollment: 1. Patients ≥18 years of age 2. Hospitalized with COVID-19 3. Enrolled within 72 hours of hospitalization OR within day 14 from first signs of illness 4. Pulmonary infiltrates on chest imaging 5. Oxygenation of \<95% on room air 6. Laboratory confirmed COVID-19
Exclusion criteria
1. Contraindication to transfusion due to inability to tolerate additional fluid, such as due to decompensated congestive heart failure 2. Baseline requirement for oxygen supplementation prior to COVID-19 infection or use of positive pressure therapy for sleep disordered breathing 3. Currently experiencing severe hypoxemic failure, as defined in study endpoints 4. Prior receipt of plasma products, IVIG, or hyperimmune globulin within past 3 months 5. Not currently enrolled another interventional clinical trial of COVID-19 treatment. Note: If taking medications with potential anti-COVID activity for the purpose of COVID-19 treatment that do not yet have data to support efficacy, such as IL-6 antagonists, these medications must be stopped prior to enrollment. Receipt of current standard of care COVID-19 treatment, including remdesivir and dexamethasone is permitted and should be recorded as a concomitant medication. Note: Pregnancy is not exclusionary but will merit additional discussion of risks & benefits in the context of ongoing pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mechanical Ventilation or Death Endpoint | Day 14 | Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mechanical Ventilation or Death Endpoint | Day 28 | Progression to mechanical ventilation or death within the first 28 days of enrollment. |
| 8-Point Ordinal Scale Endpoint | Day 29 | Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale. 8 Point WHO Ordinal Scale of Clinical Status: Uninfected (No clinical or virological evidence of infection) - 0 Ambulatory (No limitation of activities) - 1 Ambulatory (Limitation of Activities) - 2 Hospitalized Mild Disease (Hospitalized, no oxygen therapy) - 3 Hospitalized Mild Disease (Oxygen by mask or nasal prongs) - 4 Hospitalized Severe Disease (Non-invasive ventilation or high flow oxygen) - 5 Hospitalized Severe Disease (Intubation and mechanical ventilation) - 6 Hospitalized Severe Disease (Ventilation + Additional organ support (pressors, RRT, ECMO)) - 7 Dead (Death) - 8 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| COVID-19 Convalescent Plasma Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.
COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined. | 16 |
| Placebo Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.
Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2. | 18 |
| Total | 34 |
Baseline characteristics
| Characteristic | COVID-19 Convalescent Plasma | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 52 years | 57 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 23 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 10 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 19 Participants | 9 Participants |
| Race (NIH/OMB) White | 3 Participants | 8 Participants | 5 Participants |
| Region of Enrollment United States | 16 Participants | 34 Participants | 18 Participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 6 Participants | 15 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 16 | 1 / 18 |
| other Total, other adverse events | 2 / 16 | 1 / 18 |
| serious Total, serious adverse events | 2 / 16 | 1 / 18 |
Outcome results
Primary
Mechanical Ventilation or Death Endpoint
Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment.
Time frame: Day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| COVID-19 Convalescent Plasma | Mechanical Ventilation or Death Endpoint | 2 Participants |
| Placebo | Mechanical Ventilation or Death Endpoint | 0 Participants |
Secondary
8-Point Ordinal Scale Endpoint
Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale. 8 Point WHO Ordinal Scale of Clinical Status: Uninfected (No clinical or virological evidence of infection) - 0 Ambulatory (No limitation of activities) - 1 Ambulatory (Limitation of Activities) - 2 Hospitalized Mild Disease (Hospitalized, no oxygen therapy) - 3 Hospitalized Mild Disease (Oxygen by mask or nasal prongs) - 4 Hospitalized Severe Disease (Non-invasive ventilation or high flow oxygen) - 5 Hospitalized Severe Disease (Intubation and mechanical ventilation) - 6 Hospitalized Severe Disease (Ventilation + Additional organ support (pressors, RRT, ECMO)) - 7 Dead (Death) - 8
Time frame: Day 29
Population: The number of participants in the table below differs, as these are the number of participants per visit day. The number of participants decreased over the visit days as there was loss to follow up.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 20 | 6 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 22 | 8 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 1 | 2.43 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 2 | 2.15 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 3 | 3.92 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 5 | 2.83 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 6 | 2.18 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 7 | 3.4 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 8 | 5 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 9 | 4.67 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 10 | 3.67 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 11 | 5 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 12 | 5 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 13 | 3 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 14 | 2 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 15 | 6 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 16 | 6 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 17 | 6 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 18 | 6 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 19 | 6 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 21 | 8 score on a scale |
| COVID-19 Convalescent Plasma | 8-Point Ordinal Scale Endpoint | Day 4 | 3.42 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 29 | 0 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 3 | 4 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 14 | 0 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 10 | 1.8 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 1 | 1.93 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 18 | 8 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 2 | 2.14 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 11 | 2.5 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 4 | 3.69 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 15 | 0 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 5 | 2.92 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 12 | 2 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 6 | 2.45 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 17 | 8 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 7 | 3.5 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 13 | 2.5 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 8 | 2.57 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 16 | 8 score on a scale |
| Placebo | 8-Point Ordinal Scale Endpoint | Day 9 | 1.86 score on a scale |
Secondary
Mechanical Ventilation or Death Endpoint
Progression to mechanical ventilation or death within the first 28 days of enrollment.
Time frame: Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| COVID-19 Convalescent Plasma | Mechanical Ventilation or Death Endpoint | 2 Participants |
| Placebo | Mechanical Ventilation or Death Endpoint | 0 Participants |